Study of Functional Magnetic Resonance Signal Variations in Patients Undergoing Anterior Cruciate Ligament Reconstruction With the Application of a Dedicated Neuromotor Training

Variation in the volumetric activation data of the somatosensory cortex (XYZ coordinates of the peak voxel in non-overlapping brain regions) between timepoint t0 (baseline, pre-training) and timepoint t1 (post-training), measured using fMRI (BOLD sequence). This data allows for the identification of changes in brain activation attributable to the neuromotor training, supporting its effectiveness in reducing neural compensations. Based on the reference literature, a variation equal to or greater than 7 mm in the peak activation coordinates (particularly in the medio-lateral direction) will be considered clinically significant

2D kinematics (in degrees) measured using high-speed cameras on the frontal and sagittal planes, for example, within the 'Green Room' at the Isokinetic Medical Center in Bologna (a room equipped with synthetic turf, high-speed cameras, and an in-floor force platform, used for conducting functional movement tests (15, 26)). These data will allow for the evaluation of the interaction between neural input and biomechanical output following neuromotor training. A variation of at least 5° in key kinematic angles (e.g., knee valgus, lateral trunk tilt) will be considered significant, in accordance with thresholds reported in the literature.

Ground reaction forces, measured, for example, using the force platform embedded in the floor of the Isokinetic Green Room. This data will allow evaluation of the interaction between neural input and the force profile exerted on the ground during functional movements. Clinically significant variations will be considered as ≥15% compared to the pre-training value in peak vertical ground reaction force (vGRF, in Newtons) and ≥0.5*BW (force normalized to body weight).

Movement Analysis Test (MAT) score, calculated based on 2D kinematics and indicative of patient movement quality as recorded, for example, in the 'Green Room' at the Isokinetic Medical Center in Bologna. Specifically, scores of individual sub-criteria (ranging from 0 to 2), which break down movement quality through kinematic thresholds validated in the scientific literature, and the total score (sum of the 5 sub-criteria, ranging from 0 to 10) for each task will be considered. This data will allow evaluation of the interaction between somatosensory cortex activation and a composite index of movement quality across different motor tasks. Any improvement of ≥2 points in the total score (on a 0-10 scale) or ≥1 point improvement in at least three of the five sub-criteria will be considered indicative of significant functional progress, consistent with scientific validation showing a decrease in joint load (dynamic knee valgus moment) as the score increases.

Changes in functional and structural connectivity of brain networks between timepoints t0 (pre-training) and t1 (post-training) assessed using DTI and resting-state (RS) fMRI techniques. A change of ≥0.1 in Fisher z-transformed correlation coefficients between key regions of the motor network (e.g., premotor area, primary motor cortex, SMA) will be considered significant, in accordance with findings reported by Criss et al.

Serious and non-serious adverse events: Most of the events potentially associated with the procedures for outcome collection are expected to be non-serious in nature. Among non-serious adverse events, transient episodes of muscle or joint pain resulting from neuromotor training or perceived fatigue during rehabilitation sessions may occur, without leading to significant clinical consequences. Potentially serious adverse events, although unlikely, could include accidental falls during physical activity causing significant trauma that would require immediate cessation of the procedure and medical intervention.